Faculty Opinions recommendation of Exportin-5-mediated nuclear export of eukaryotic elongation factor 1A and tRNA.

2002 ◽  
Author(s):  
Anita Hopper
Keyword(s):  
Nuclear Export ◽  
Elongation Factor ◽  
Eukaryotic Elongation Factor

scholarly journals Exportin-5-mediated nuclear export of eukaryotic elongation factor 1A and tRNA

2002 ◽  
Vol 21 (22) ◽  
pp. 6216-6224 ◽  
Author(s):  
Angelo Calado ◽  
Nathalie Treichel ◽  
Eva-Christina Müller ◽  
Albrecht Otto ◽  
Ulrike Kutay
Keyword(s):  
Nuclear Export ◽  
Elongation Factor ◽  
Eukaryotic Elongation Factor

scholarly journals Consecutive interactions with HSP90 and eEF1A underlie a functional maturation and storage pathway of AID in the cytoplasm

2015 ◽  
Vol 212 (4) ◽  
pp. 581-596 ◽  
Author(s):  
Stephen P. Methot ◽  
Ludivine C. Litzler ◽  
Felipe Trajtenberg ◽  
Astrid Zahn ◽  
Francis Robert ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Elongation Factor ◽  
Chromosomal Translocation ◽  
Heat Shock Protein 90 ◽  
Free Form ◽  
Translation Elongation ◽  
Class Switch ◽  
Eukaryotic Elongation Factor ◽  
Activation Induced Deaminase ◽  
Functional Relevance

Activation-induced deaminase (AID) initiates mutagenic pathways to diversify the antibody genes during immune responses. The access of AID to the nucleus is limited by CRM1-mediated nuclear export and by an uncharacterized mechanism of cytoplasmic retention. Here, we define a conformational motif in AID that dictates its cytoplasmic retention and demonstrate that the translation elongation factor eukaryotic elongation factor 1 α (eEF1A) is necessary for AID cytoplasmic sequestering. The mechanism is independent of protein synthesis but dependent on a tRNA-free form of eEF1A. Inhibiting eEF1A prevents the interaction with AID, which accumulates in the nucleus and increases class switch recombination as well as chromosomal translocation byproducts. Most AID is associated to unspecified cytoplasmic complexes. We find that the interactions of AID with eEF1A and heat-shock protein 90 kD (HSP90) are inversely correlated. Despite both interactions stabilizing AID, the nature of the AID fractions associated with HSP90 or eEF1A are different, defining two complexes that sequentially produce and store functional AID in the cytoplasm. In addition, nuclear export and cytoplasmic retention cooperate to exclude AID from the nucleus but might not be functionally equivalent. Our results elucidate the molecular basis of AID cytoplasmic retention, define its functional relevance and distinguish it from other mechanisms regulating AID.

scholarly journals Scyl1 Facilitates Nuclear tRNA Export in Mammalian Cells by Acting at the Nuclear Pore Complex

2010 ◽  
Vol 21 (14) ◽  
pp. 2483-2499 ◽  
Author(s):  
Shawn C. Chafe ◽  
Dev Mangroo
Keyword(s):  
Nuclear Pore Complex ◽  
Protein Trafficking ◽  
Nuclear Export ◽  
Mammalian Cells ◽  
Biochemical Characterization ◽  
Elongation Factor ◽  
Nuclear Pore ◽  
Eukaryotic Elongation Factor ◽  
Quaternary Complex

Scyl1 is an evolutionarily conserved N-terminal protein kinase-like domain protein that plays a role in COP1-mediated retrograde protein trafficking in mammalian cells. Furthermore, loss of Scyl1 function has been shown to result in neurodegenerative disorders in mice. Here, we report that Scyl1 is also a cytoplasmic component of the mammalian nuclear tRNA export machinery. Like exportin-t, overexpression of Scyl1 restored export of a nuclear export-defective serine amber suppressor tRNA mutant in COS-7 cells. Scyl1 binds tRNA saturably, and associates with the nuclear pore complex by interacting, in part, with Nup98. Scyl1 copurifies with the nuclear tRNA export receptors exportin-t and exportin-5, the RanGTPase, and the eukaryotic elongation factor eEF-1A, which transports aminoacyl-tRNAs to the ribosomes. Scyl1 interacts directly with exportin-t and RanGTP but not with eEF-1A or RanGDP in vitro. Moreover, exportin-t containing tRNA, Scyl1, and RanGTP form a quaternary complex in vitro. Biochemical characterization also suggests that the nuclear aminoacylation-dependent pathway is primarily responsible for tRNA export in mammalian cells. These findings together suggest that Scyl1 participates in the nuclear aminoacylation-dependent tRNA export pathway and may unload aminoacyl-tRNAs from the nuclear tRNA export receptor at the cytoplasmic side of the nuclear pore complex and channels them to eEF-1A.

scholarly journals Crystal Structure of Exotoxin A from Aeromonas Pathogenic Species

Toxins ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 397 ◽  
Author(s):  
Geoffrey Masuyer
Keyword(s):  
Crystal Structure ◽  
Metal Binding ◽  
Elongation Factor ◽  
Pathogenic Species ◽  
Exotoxin A ◽  
Pseudomonas Exotoxin A ◽  
Eukaryotic Elongation Factor 2 ◽  
Eukaryotic Elongation Factor ◽  
Bacterial Virulence Factor ◽  
Interdomain Interactions

Aeromonas exotoxin A (AE) is a bacterial virulence factor recently discovered in a clinical case of necrotising fasciitis caused by the flesh-eating Aeromonas hydrophila. Here, database mining shows that AE is present in the genome of several emerging Aeromonas pathogenic species. The X-ray crystal structure of AE was solved at 2.3 Å and presents all the hallmarks common to diphthamide-specific mono-ADP-ribosylating toxins, suggesting AE is a fourth member of this family alongside the diphtheria toxin, Pseudomonas exotoxin A and cholix. Structural homology indicates AE may use a similar mechanism of cytotoxicity that targets eukaryotic elongation factor 2 and thus inhibition of protein synthesis. The structure of AE also highlights unique features including a metal binding site, and a negatively charged cleft that could play a role in interdomain interactions and may affect toxicity. This study raises new opportunities to engineer alternative toxin-based molecules with pharmaceutical potential.

scholarly journals On the Need to Tell Apart Fraternal Twins eEF1A1 and eEF1A2, and Their Respective Outfits

2021 ◽  
Vol 22 (13) ◽  
pp. 6973
Author(s):  
Alberto Mills ◽  
Federico Gago
Keyword(s):  
De Novo ◽  
Elongation Factor ◽  
Missense Mutations ◽  
Developmentally Regulated ◽  
High Sequence Identity ◽  
80S Ribosome ◽  
Cellular Effects ◽  
Cellular Processes ◽  
Eukaryotic Elongation Factor ◽  
A Site

eEF1A1 and eEF1A2 are paralogous proteins whose presence in most normal eukaryotic cells is mutually exclusive and developmentally regulated. Often described in the scientific literature under the collective name eEF1A, which stands for eukaryotic elongation factor 1A, their best known activity (in a monomeric, GTP-bound conformation) is to bind aminoacyl-tRNAs and deliver them to the A-site of the 80S ribosome. However, both eEF1A1 and eEF1A2 are endowed with multitasking abilities (sometimes performed by homo- and heterodimers) and can be located in different subcellular compartments, from the plasma membrane to the nucleus. Given the high sequence identity of these two sister proteins and the large number of post-translational modifications they can undergo, we are often confronted with the dilemma of discerning which is the particular proteoform that is actually responsible for the ascribed biochemical or cellular effects. We argue in this review that acquiring this knowledge is essential to help clarify, in molecular and structural terms, the mechanistic involvement of these two ancestral and abundant G proteins in a variety of fundamental cellular processes other than translation elongation. Of particular importance for this special issue is the fact that several de novo heterozygous missense mutations in the human EEF1A2 gene are associated with a subset of rare but severe neurological syndromes and cardiomyopathies.

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